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Journal of Clinical Oncology, Vol 23, No 1 (January 1), 2005: pp. 246-247 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.197
In Reply:Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India We appreciate the opportunity to respond to the letter concerning our article "Consolidation Radiation After Complete Remission in Hodgkin's Disease Following Six Cycles of ABVD Chemotherapy: Is There a Need?"1 There are two basic approaches to optimizing treatment outcomes in Hodgkin's disease: risk-adapted versus response-adapted. A closer look at the Norton Simon model (incorporating the Gompertzian kinetics and the log-kill hypothesis) reveals that even after a complete response (CR) is achieved clinically with combination chemotherapy, there exists substantial subclinical disease burden that can cause a relapse.2 This subclinical disease can possibly be eradicated by another two log kills, prompting the use of two more cycles of chemotherapy after CR as consolidation. Since advanced Hodgkin's disease generally necessitates six cycles of chemotherapy for achieving CR, the eight-cycle recommendation may be considered standard for the risk-adapted approach, although it has never been validated in large controlled trials. There is no such eight-cycle recommendation for the response-adapted strategy, where the number of chemotherapy cycles should be dictated by the response to treatment as a reflection of biology of disease. The European Organisation for the Research and Treatment of Cancer Lymphoma Group chose a response-adapted induction chemotherapy approach with a different design.3 They continued the MOPP-ABV (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) hybrid regimen for two more cycles after CR, irrespective of the CR being achieved early (four cycles) or later (six cycles). Patients with less than a CR even after six cycles of chemotherapy were treated with radiation therapy. Thus, all patients with CR underwent random assignment to low-dose involved-field radiotherapy or observation only after receiving two cycles of consolidation chemotherapy. We still maintain that since they had already received some form of consolidation, the benefit of additional radiation was not forthcoming. In contrast, we used a fixed number of cycles (six cycles) for all stages of Hodgkin's disease1 due to the prevalent institutional policy at that time. Herein on subset analysis, the benefit of consolidation radiation was not evident in early-stage disease. This may be partly explained by the fact that a substantial number of these early-stage patients could have achieved an early CR (after two to four cycles), rendering additional radiation redundant. Nonetheless, we do agree that results of unplanned cohort analysis should be interpreted with caution and that the required number of chemotherapy cycles may be different for different stages of Hodgkin's disease. In keeping with the aforementioned, we are presently randomly assigning eligible early-stage patients stratified on known risk factors to two versus four cycles of ABVD followed by radiotherapy. We strongly believe that some form of consolidation therapy is necessary after CR in advanced Hodgkin's disease to maintain remission. There is ample evidence suggesting that low-dose involved-field radiotherapy is comparable to consolidation chemotherapy in that regard.4 However, with the concerns regarding the potential late effects of radiation, many investigators preferentially use chemotherapy for consolidation.5 The benefit of consolidation radiation in dose-intensive chemotherapy regimens remains to be defined. However, radiotherapy still continues to be a part of standard protocol in advanced Hodgkin's disease for major groups such as Stanford and Milan.6 Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Laskar S, Gupta T, Vimal S, et al: Consolidation radiation after complete remission in Hodgkin's disease following six cycles of ABVD chemotherapy: Is there a need? J Clin Oncol 22:62-68, 2004 2. Norton L: The Norton Simon hypothesis, in Perry MC (ed): Cancer Chemotherapy Handbook (ed 2). Norwalk, CT, Appleton & Lange, 1994, pp3-14
3. Aleman B, Raemekers J, Tirelli U, et al: Involved field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 348:2396-2406, 2003
4. Ferme C, Sebban C, Hennequin C, et al: Comparison of chemotherapy to radiotherapy as consolidation of complete or good partial response after six cycles of chemotherapy for patients with advanced Hodgkin's disease: Results of the Groupe d'Etudes des Lymphomas de l'Adulte H89 trial. Blood 95:2246-2252, 2000
5. Diehl V, Loeffler M, Pfreundschuh M, et al: Further chemotherapy versus low dose involved field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advanced Hodgkin's disease. German Hodgkin's Study Group (GHSG). Ann Oncol 6:901-910, 1995 6. Prosnitz LR: Consolidation radiotherapy in the treatment of Advanced Hodgkin's disease: Is it dead? Int J Radiat Oncol Biol Phys 56:605-608, 2003[CrossRef][Medline]
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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